Using diffusion MRI data acquired with ultra-high gradient strength to improve tractography in routine-quality data.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.

[Secondary surgeries in craniosynostosis and faciocraniosynostosis]. / Chirurgie secondaire des craniosténoses et faciocraniosténoses.

Secondary surgeries for single craniosynostosis surgeries are mainly esthetic refinements rather than functional indications. However, cranioplasties for bone defects correction or insufficient corrections may be undertaken. Management of syndromic craniosynostoses usually requires multiple surgical interventions, the sequence of which might vary per the genetic mutation. It is commonplace to start with posterior vault expansion before age 6 months, then treat cerebellar tonsillar herniation by the age of twelve months, and delay fronto-facial monobloc advancement until at least 18-24 months of age. Ventricular shunting is preferably avoided or delayed. Failure to respect these guidelines can significantly complicate the subsequent management. Primary fronto-orbital advancement or early facial osteotomy type Le Fort3, may compromise the subsequent fronto-facial monobloc advancement. However, this salvage secondary monobloc may be undertaken in some instances despite previous anterior osteotomies with a higher morbidity.

Reduced focal fiber collinearity in the cingulum bundle in adults with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a disabling condition, often associated with a chronic course. Given its role in attentional control, decision-making, and emotional regulation, the anterior cingulate cortex is considered to have a key role in the pathophysiology of the disorder. Notably, the cingulum bundle, being the major white matter tract connecting to this region, has been historically a target for the surgical treatment of intractable OCD. In this study, we aimed to identify the extent to which focal-more than diffuse-abnormalities in fiber collinearity of the cingulum bundle could distinguish 48 adults with OCD (mean age [SD] = 23.3 [4.5] years; F/M = 30/18) from 45 age- and sex-matched healthy control adults (CONT; mean age [SD] = 23.2 [3.8] years; F/M = 28/17) and further examine if these abnormalities correlated with symptom severity. Use of tract-profiles rather than a conventional diffusion imaging approach allowed us to characterize white matter microstructural properties along (100 segments), as opposed to averaging these measures across, the entire tract. To account for these 100 different segments of the cingulum bundle, a repeated measures analysis of variance revealed a main effect of group (OCD < CONT; F[1,87] = 5.3; P = 0.024) upon fractional anisotropy (FA, a measure of fiber collinearity and/or white matter integrity), in the cingulum bundle, bilaterally. Further analyses revealed that these abnormalities were focal (middle portion) within the left and right cingulum bundle, although did not correlate with symptom severity in OCD. Findings indicate that focal abnormalities in connectivity between the anterior cingulate cortex and other prefrontal cortical regions may represent neural mechanisms of OCD.

The place of dopamine in the cortico-basal ganglia circuit.

The midbrain dopamine (DA) neurons play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. Indeed, subpopulations of DA neurons have been associated with these different functions: the mesolimbic, mesocortical, and nigrostriatal pathways. The mesolimbic and nigrostriatal pathways are an integral part of the basal ganglia through its reciprocal connections to the ventral and dorsal striatum respectively. This chapter reviews the connections of the midbrain DA cells and their role in integrating information across limbic, cognitive and motor functions. Emphasis is placed on the interface between these functional domains within the striatum through corticostriatal connections, through the striato-nigro-striatal connection, and through the lateral habenula projection to the midbrain.

Organized breast screening: Answers to recurring controversies.

The reduction in mortality specifically from breast cancer, demonstrated in the major meta-analyses in the 1980s resulted in public health breast cancer screening programs being set up in many countries, including France. Recent publications have challenged the usefulness of screening, by insisting in particular on the negative effects of overdiagnosis and the lack of any significant impact on mortality. From analysis of the literature and particularly independent reviews published in 2012, we provide some answers for doctors faced with the legitimate concerns of women. These studies confirm that screening in the right age group reduces specific mortality by at least 20% at a cost of overdiagnosis estimated at between 1 and 15%.

Temperature-Sensitive Resistance to Wheat streak mosaic virus in CO960333 and KS06HW79 Wheat.

Temperature-sensitive resistance (TSR) that can protect against losses to Wheat streak mosaic virus (WSMV) has been described in elite wheat germplasm. A TSR identified in the advanced breeding line CO960333 and its derivative KS06HW79 was examined in growth-chamber tests conducted under constant temperature regimes of 18, 21, and 24°C against an array of WSMV isolates. At 18°C, all tested isolates systemically infected the pedigree parents, while the progeny line CO960333 remained free of symptoms; at 24°C, all lines were susceptible. At the intermediate temperature of 21°C, the TSR of KS06HW79 was effective in contrast to the TSRs of KS03HW12 and 'RonL'. In field trials conducted in 2011 and 2012, the TSR expressed in KS06HW79 conferred complete protection against yield losses from inoculation with the Sidney 81 isolate of WSMV, while the TSR of RonL conferred similar protection in 2012 but allowed small losses in 2011. The resistance expressed by KS06HW79 is likely not due to the Wsm1 gene because it did not contain the tightly linked J15 sequence-characterized amplified region (SCAR) DNA marker. These findings suggest that KS06HW79 could be an additional TSR source of value to wheat-breeding programs seeking to control losses from WSMV.

Low-Reynolds-number swimmer utilizing surface traveling waves: analytical and experimental study.

Microscale slender swimmers are frequently encountered in nature and are now used in microrobotic applications. The swimming mechanism examined in this paper is based on small transverse axisymmetric traveling wave deformations of a cylindrical long shell. The thin-shelled device is assumed to be inextensible at the middle surface and extensible at the surface wetted by the fluid. Assuming low-Reynolds-number hydrodynamics, an analytical solution is derived for waves of small amplitudes compared with the cylinder diameter. We show that swimming velocity increases with ß(1) (the ratio of cylinder radius to wavelength) and that swimming velocity is linearly dependent on wave propagation velocity, increasing to leading order with the square of the ratio of wave amplitude to wavelength ß(2) and decreasing with the wall thickness. A fourth-order correction in ß(2) was also calculated and was found to have a negative effect on the swimming velocity. The results for a shell of negligible-wall thickness were compared with Taylor's solution for an inextensible two-dimensional flat membrane undergoing a waving motion and Felderhof's results [Phys. Fluids 22, 113604 (2010)] for an unbounded flow field and negligible-wall thickness. We show that Taylor's analytic solution is a particular limiting case of the present solution, assuming zero wall thickness and infinite values of ß(1). The present mechanism was also compared with Taylor's well known solutions of waving planar and helical circular tails. We show that the present approach yields higher velocities as ß(1) increases, whereas, the opposite occurs for waving tails. Indeed, in the region where ß(1)>15, the present approach yields velocities nearly as fast as Taylor's helical waving tail while consuming less power and with a design that is considerably more compact. In this regime, the axisymmetric swimmer is twice as fast as Taylor's planar-tail swimmer for an additional investment of only one-third of the power. Experiments were conducted using a macroscale autonomous model immersed in highly viscous silicone fluid. We outlined how the proposed mechanism was realized to propel an elongated, yet finite, swimmer. Measured data demonstrate the effects of wave velocity and wavelength on swimming speed, showing good agreement with analytical results.

The simultaneous role of an alveolus as flow mixer and flow feeder for the deposition of inhaled submicron particles.

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps' dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus.

Identification of Variants of the High Plains virus Infecting Wheat in Kansas.

The properties of two virus isolates (U04-82 and U04-83) obtained from two wheat (Triticum aestivum) plants expressing mosaic symptoms were investigated using enzyme-linked immunosorbent assay (ELISA), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), time-of-flight mass spectrometry (TOFMS), and infection of wheat with resistance to Wheat streak mosaic virus (WSMV). The coat protein mass was estimated by SDS-PAGE as approximately 32 kDa for U04-82 and 30 kDa for U04-83. The amino acid sequence of the coat protein of U04-82 was 99.6 and 85.5% identical to two isolates, ABC58222 and TX96, respectively, of High Plains virus (HPV) described from Texas. U04-82 was transmitted by wheat curl mites and caused significant yield reductions in wheat resistant to WSMV. U04-83 was actually two distinct virus isolates whose capsid protein amino acid sequences were only 57 and 50% similar to that of TX96. Antiserum prepared to a synthetic peptide from the sequence of the U04-83 isolate recognized the two U04-83 isolates, but not the U04-82 isolate.

Interactions of blood cell constituents: experimental investigation and computational modeling by discrete particle dynamics algorithm.

When the size of individual blood constituents [e.g., red blood cells (RBCs), white blood cells, platelets] becomes comparable to the size of blood vessels, the interactions among blood constituents in determining the blood behavior can no longer be ignored. In this paper, we have developed a comprehensive computational model to simulate the motion of an individual platelet in the plasma medium and its binding to the microvessel wall. The model is based on a Discrete Particle Dynamics (DPD) algorithm, in which blood plasma, platelets and the vessel walls are treated as a group of discretized mesoscopic size particles interacting through conservative, dissipative and random forces. Deposition (i.e., binding) of platelets is modeled by considering attractive forces at the vessel wall, which is characterized by the values of the effective spring constant for platelet adhesion. To test this model, we simulated platelet deposition in a perfusion chamber. By matching the simulation results to experimental data, the effective platelet spring constants were determined and were found to be approximately 50 N/m, which is within a physiologically relevant range. It is demonstrated that the DPD analysis offers the capability of simulating the time-dependent binding of platelets. We conclude that this model provides a new approach for studying the interaction among blood constituents.

Temperature-Sensitive Wheat streak mosaic virus Resistance Identified in KS03HW12 Wheat.

Wheat streak mosaic virus (WSMV) infection reduces seed yield and quality in wheat. These losses can be alleviated significantly by exploiting genetic host plant resistance. A new source of temperature-sensitive resistance to WSMV, KS03HW12, and its parental lines (KS97HW29/ KS97HW131//KS96HW100-5) were evaluated in both greenhouse and field conditions. Parental wheat lines were exposed to WSMV pressure under different temperatures in growth chambers to determine the stability of the resistance, and 2 years of field yield trials were conducted to confirm effectiveness. To determine the effectiveness of its resistance against a spectrum of isolates, KS03HW12 was tested against six different WSMV isolates of different geographic origins. Among the three pedigree parents, only one, KS97HW29, was resistant. The parental lines of KS97HW29 are not available for testing; therefore, the presumed origin of the resistance could not be further confirmed. None of the six tested WSMV isolates systemically infected KS03HW12 at 18°C. Yield of KS03HW12 in field tests was not different from healthy controls. Thus, the elite winter wheat KS03HW12 appears to be a stable and effective source of temperature-sensitive resistance to WSMV and should be useful for wheat breeding programs.

Dissipative particle dynamics simulation of flow generated by two rotating concentric cylinders: boundary conditions.

The dissipative particle dynamics (DPD) method was used to simulate the flow in a system comprised of a fluid occupying the space between two cylinders rotating with equal angular velocities. The fluid, initially at rest, ultimately reaches a steady, linear velocity distribution (a rigid-body rotation). Since the induced flow field is solely associated with the no-slip boundary condition at the walls, we employed this system as a benchmark to examine the effect of bounce-back reflections, specular reflections, and Pivkin-Karniadakis no-slip boundary conditions, upon the steady-state velocity, density, and temperature distributions. An additional advantage of the foregoing system is that the fluid occupies inherently a finite bounded domain so that the results are affected by the prescribed no-slip boundary conditions only. Past benchmark systems such as Couette flow between two infinite parallel plates or Poiseuille flow in an infinitely long cylinder must employ artificial periodic boundary conditions at arbitrary upstream and downstream locations, a possible source of spurious effects. In addition, the effect of the foregoing boundary conditions on the time evolution of the simulated velocity profile was compared with that of the known, time-dependent analytical solution. It was shown that bounce-back reflection yields the best results for the velocity distributions with small fluctuations in density and temperature at the inner fluid domain and larger deviations near the walls. For the unsteady solutions a good fit is obtained if the DPD friction coefficient is proportional to the kinematic viscosity. Based on dimensional analysis and the numerical results a universal correlation is suggested between the friction coefficient and the kinematic viscosity.

Panic and fear induced by deep brain stimulation.

BACKGROUND: Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region. OBJECTIVE: To investigate panic and fear resulting from DBS. METHODS: Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions. RESULTS: DBS at the distal (0) contact (cathode 0-, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off condition CONCLUSIONS: DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks.

Temperature Sensitivity and Efficacy of Wheat streak mosaic virus Resistance Derived from CO960293 Wheat.

Wheat yields often are limited by infection by Wheat streak mosaic virus (WSMV). Host plant resistance to WSMV can reduce losses. This study was conducted to characterize a new source of temperature-sensitive resistance found in CO960293 wheat. The source of the temperature-sensitive resistance in CO960293 is unknown. Parental and other wheat lines were tested for WSMV resistance using 51 WSMV isolates under different temperatures to determine the stability of the resistance, and yield trials were conducted in the field for 3 years. All parental wheat lines became infected by WSMV at all temperatures and were infective in back assay to 'Tomahawk' wheat. No WSMV isolate defeated the resistance of CO960293 at 18°C. Yield of CO960293 in field trials was reduced in only 1 of 3 years. Our data demonstrate that this wheat line can be a valuable source of resistance to WSMV in wheat programs, particularly in areas where temperatures are cool following planting in the fall.

Characterization of a distinct Johnsongrass mosaic virus strain isolated from sorghum in Nigeria.

A virus isolated from sorghum in Nigeria has been partially characterized. It was tested by enzyme-linked immunosorbent assay (ELISA) using antisera to Maize dwarf mosaic virus, Johnsongrass mosaic virus (JGMV), Sugarcane mosaic virus strain-MDB, Sorghum mosaic virus, and Zea mosaic virus. A partial host range, symptom phenotypes for selected sorghum lines, and the mass of the coat protein (CP) subunit was analyzed by sodium-dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and its amino acid (aa) sequence determined by time-of-flight mass spectrometry (TOFMS). The Nigerian isolate was positive in ELISA to only JGMV antiserum. It infected sorghum and smooth brome but not oat or johnsongrass. It caused necrosis in 12 of 13 tested sorghum lines, while the USA JGMV isolate caused necrosis in only one sorghum line. In SDS-PAGE, the mass of the Nigerian virus CP was 3,000 Da smaller than that of JGMV-MDO. Moreover, TOFMS analyses showed that, while residues 1-7 of the CP aa sequence were identical to those of JGMV (GenBank #A27631), and residues 57-293 were almost identical to residues 67-303 of JGMV, the intermediate region exhibited significant differences, including a 10 aa deletion. These data indicate that the virus should be considered a distinct isolate of JGMV (JGMV-N) and expands the known range of JGMV to Africa.

[Study on the management of patients following detection of a "probably benign" mammographic abnormality (ACR BI-RADS category 3): a review of 176 radiologists]. / Une étude exploratoire des pratiques et des comportements radiologiques devant la découverte d'une anomalie "probablement bénigne" sur la mammographie: à propos de 176 radiologues.

OBJECTIVES: To evaluate mid-term management of patients with category 3 findings (probably benign, ACR BI-RADS) at mammography three months after a CME course on breast cancer. METHODS: A questionnaire (33 items) was sent to 529 radiologists, three months after the CME course (May-December 2002). The answers were analysed using the chi-square test. RESULTS: A total of 176 radiologists completed the questionnaire; 63 were part of an organized screening mammography program; 162 used the BI-RADS classification. In the presence of a class 3 finding, 158 radiologists recommended short term follow-up, 28 recommended biopsy, 9 upgraded the level of abnormality, 116 consulted another radiologist, 42 consulted an expert mammographer, 36 submitted the case to a multidisciplinary committee and 12 asked for an overread. Management with short term interval follow-up was worrisome to 91 radiologists for fear of unfavorable outcome, and to 47 radiologists because of possible litigation. Twenty-six radiologists had difficulty explaining to patients the need for short term follow-up. The median score for perceived stress by the radiologists was 3 (0=low and 10=high). CONCLUSION: The practices of this sample of French radiologists are consistent with the recommendations presented during the CME course and by the ANAES. They may have some difficulty in communicating with patients the need for follow-up. The ethics of radiology are based on "primum non nocere".

Biological and Molecular Variability Among High Plains virus Isolates.

The High Plains virus (HPV), vectored by the wheat curl mite (WCM) (Aceria tosichella), causes a severe disease of maize (Zea mays) in the U. S. High Plains. In the present study, five HPV isolates from five states were separated from co-infecting Wheat streak mosaic virus and their molecular and biological variability studied. Molecular studies involved time-of-flight mass spectrometry (TOFMS) to determine amino acid sequence variability of the 32-kDa nucleoprotein (32 np) of the isolates. Biological studies involved testing the ability of the five HPV isolates to infect a maize line previously shown to have resistance. Inoculations of the HPV isolates were conducted using vascular puncture inoculation (VPI) and viruliferous WCM. TOFMS analyses demonstrated an 18-amino acid sequence in the isolates at the N-terminus of the 32 np, the presence of amino acid sequence differences among the isolates, and variability among amino acid sequences of the 32 np of some isolates. Three of the five HPV isolates infected the resistant maize inbred, B73, using VPI, and two of the same three HPV isolates infected this line using WCM inoculation, albeit low numbers of plants were infected by each technique.

Restricted daily consumption of a highly palatable food (chocolate Ensure(R)) alters striatal enkephalin gene expression.

Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, and the control of food intake. Opioid peptides within the ventral striatum are thought to play a key role in the latter function, regulating the affective response to highly palatable, energy-dense foods such as those containing fat and sugar. It has been shown previously that stimulation of mu opiate receptors within the ventral striatum increases intake of palatable food. In the present study, we examined enkephalin peptide gene expression within the striatum in rats that had been given restricted daily access to an energy-dense, palatable liquid food, chocolate Ensure(R). Rats maintained on an ad libitum diet of rat chow and water were given 3-h access to Ensure(R) daily for two weeks. One day following the end of this period, preproenkephalin gene expression was measured with quantitative in situ hybridization. Compared with control animals, rats that had been exposed to Ensure(R) had significantly reduced enkephalin gene expression in several striatal regions including the ventral striatum (nucleus accumbens), a finding that was confirmed in a different group with Northern blot analysis. Rats fed this regimen of Ensure(R) did not differ in weight from controls. In contrast to chronic Ensure(R), acute ingestion of Ensure(R) did not appear to affect enkephalin peptide gene expression. These results suggest that repeated consumption of a highly rewarding, energy-dense food induces neuroadaptations in cognitive-motivational circuits.

Gravitational deposition in a rhythmically expanding and contracting alveolus.

In a previous simulation, our laboratory demonstrated that the flow induced by a rhythmically expanding and contracting alveolus is highly complex (Haber S, Butler JP, Brenner H, Emanuel I, and Tsuda A, J Fluid Mech 405: 243-268, 2000). Based on these earlier findings, we hypothesize that the trajectories and deposition of aerosols inside the alveoli differ substantially from those previously predicted. To test this hypothesis, trajectories of fine particles (0.5-2.5 microm in diameter) moving in the foregoing alveolar flow field and simultaneously subjected to the gravity field were simulated. The results show that alveolar wall motion is crucial in determining the enhancement of aerosol deposition inside the alveoli. In particular, 0.5- to 1-microm-diameter particles are sensitive to the detailed alveolar flow structure (e.g., recirculating flow), as they undergo gravity-induced convective mixing and deposition. Accordingly, deposition concentrations within each alveolus are nonuniform, with preferentially higher densities near the alveolar entrance ring, consistent with physiological observations. Deposition patterns along the acinar tree are also nonuniform, with higher deposition in the first half of the acinar generations. This is a result of the combined effects of enhanced alveolar deposition in the proximal region of the acinus due to alveoli expansion and contraction and reduction in the number of particles remaining in the gas phase down the acinar tree. We conclude that the cyclically expanding and contracting motion of alveoli plays an important role in determining gravitational deposition in the pulmonary acinus.